Seasonal influenza is the cause of tens to hundreds of thousands of human deaths each year.[1] However, of particular concern is the threat of a pandemic caused by the influenza virus crossing from animal species. A recent example of such an influenza pandemic is the influenza A (H1N1) ‘swine flu’ outbreak of 2009 which caused high morbidity and, in some cases, severe disease and mortality.
The influenza virus has two types of surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA). The HA recognizes sialic acids present on the surface of host cells and binds to these carbohydrates in order to infect the cell and the NA releases progeny virus from the infected cell.[2] Measures to prevent a new influenza virus pandemic involve both vaccination and antiviral drugs, the latter ideally administered within 48 h of the infection.[3]
The effective use of antivirals requires rapid and early diagnosis. Current methods for the detection of influenza include: molecular identification of influenza isolates including reverse-transcription PCR, immunofluorescence antibody staining, virus isolation in cell culture or in embryonated chicken eggs, and serological diagnosis by haemagglutination inhibition or by microneutralization.[3b] All of these methods are time-consuming, taking several hours or even days for results to be obtained, and also require specialist equipment and trained analysts.
Gold nanoparticles (ca. 16 nm in diameter) in aqueous suspension exhibit an intense red color due to their surface plasmon absorption band. This optical property is distance-dependent and upon aggregation of the metal nanoparticles the solution changes color. The color change, readily observed with the naked eye, is due to the coupling interactions between the surface plasmon fields of the particles. Gold nanoparticle-based colorimetric assays have been reported [4] for the detection of a variety of species, including oligonucleotides, metal ions, anions, small organic molecules and proteins, a field reviewed recently by Rotello et al.[5] By functionalizing metal nanoparticles with specifically synthesized carbohydrate ligands, glyconanoparticles can be created.[6] Glyconanoparticle-based colorimetric assays have been used for the detection of lectins, calcium ions, and cholera toxin.[7]
Gold nanoparticles have been used for the inhibition of influenza virus. Papp et al. employed 14 nm gold nanoparticles functionalized with a sialic-acid-terminated glycerol dendron to inhibit X31 influenza virus (a reassortant H3N2 influenza virus carrying the HA and NA genes of A/Aichi/2/68).[8] In addition, gold nanoparticles coated with a phosphonate ester analogue of the influenza therapeutic Oseltamivir,[9] with mercaptoethanesulfonate and mercaptosuccinic acid,[10] and gold nanorods functionalized with ssRNA[11] have also been used for the inhibition of influenza virus.
Gold nanoparticles have also been used for the detection of influenza virus. Influenza A/Puerto Rico/8/34 (PR8) (H1N1) virus has been detected using antibody-functionalized gold nanoparticles and dynamic light scattering.[12] Gold nanoparticles functionalized with a chemically unmodified monomer of sialic acid have been used to colorimetrically detect influenza B viruses of the B/Victoria and B/Yamagata lineages through the interaction between the sialic acid and the HA on the virus.[13]
US 2008/0194801 relates to a reportedly novel library of compounds comprising a spacer with an attachment element on one terminus and a recognition element on the other terminus. The library of compounds can be attached to a solid support and used in sensors and biosensors.
WO 2011/130332 relates to glycan arrays that bind specific target HAs and are reported to detect and distinguish between various sub-types and strains of influenza virus. Methods for using the glycan arrays with assays using nanoparticle amplification technique are also reportedly disclosed.
WO2008/123844 relates to a method and system for detecting magnetic nanoparticles include measuring a magneto-optical enhancement of TP the plasmon absorption in the optical response.
US 2012/0015344 relates to a particulate composition formed from a conductive polymer bound to magnetic nanoparticles. The particulate composition can be formed into a biologically enhanced, electrically active magnetic (BEAM) nanoparticle composition by further including a binding pair member (e.g., an antibody or a fragment thereof that specifically recognizes a virus strain or a virus surface protein) bound to the conductive polymer of the particulate composition. Notwithstanding the above it can be seen that a rapid, diagnostic test that is simple to perform, works on unpurified samples, and is ideally able to discriminate between human influenza and emerging animal strains, such as the avian H5N1 ‘bird flu’ virus that has generated considerable concern following its re-emergence in 2003-2004 or the avian H7N9 transmitted to humans in 2013, would provide a contribution to the art.